Central Tolerance

Definition

Central tolerance is a critical immunological process that occurs during the development of immune cells, primarily in the thymus for T cells and in the bone marrow for B cells. This mechanism ensures that developing lymphocytes do not react against the body's own tissues, thereby preventing autoimmunity and promoting self-tolerance.

5 Must Know Facts For Your Next Test

1. Central tolerance primarily takes place in the thymus for T cells and in the bone marrow for B cells, where developing cells undergo selection processes.
2. In T cell development, both positive and negative selection are essential; positive selection ensures survival of functional cells, while negative selection eliminates self-reactive ones.
3. B cells also experience a form of central tolerance through receptor editing or deletion when they encounter self-antigens during their development in the bone marrow.
4. Failure of central tolerance mechanisms can lead to autoimmune diseases as self-reactive lymphocytes escape into circulation and can initiate immune responses against self-tissues.
5. Research suggests that central tolerance is not absolute; some autoreactive lymphocytes can still persist, which highlights the importance of peripheral tolerance mechanisms to control these potentially harmful cells.

Review Questions

• How does central tolerance contribute to the prevention of autoimmunity during T cell development?
  • Central tolerance plays a vital role in preventing autoimmunity by ensuring that T cells that recognize self-antigens are eliminated during their development in the thymus. Through negative selection, thymocytes that strongly bind to self-antigens undergo apoptosis, thus preventing them from maturing into potentially harmful effector T cells. This selective process helps maintain a pool of T cells that can respond to foreign pathogens without attacking the body’s own tissues.
• Discuss the differences between positive selection and negative selection in the context of central tolerance.
  • Positive selection occurs first in T cell development, where thymocytes that can moderately bind to self-MHC molecules are given survival signals to mature into functional T cells. Conversely, negative selection follows, removing those thymocytes that have a high affinity for self-antigens, thereby preventing them from becoming autoreactive. Together, these processes ensure that only those T cells capable of recognizing foreign antigens without attacking self-tissues successfully mature.
• Evaluate the implications of a breakdown in central tolerance mechanisms on overall immune system function and disease manifestation.
  • A breakdown in central tolerance mechanisms can lead to the escape of autoreactive lymphocytes into circulation, increasing the risk of autoimmune diseases such as lupus or rheumatoid arthritis. When self-reactive T or B cells are not adequately eliminated during their development, they may initiate inappropriate immune responses against the body’s own tissues. This highlights how crucial central tolerance is for maintaining immune homeostasis and preventing disease, emphasizing the need for both central and peripheral tolerance mechanisms to work together effectively.

Related terms

Negative Selection:

A process during T cell development where thymocytes that strongly recognize self-antigens are induced to undergo apoptosis, ensuring that only non-autoreactive T cells mature.

Positive Selection:

The stage in T cell maturation where thymocytes that can adequately recognize self-MHC molecules receive survival signals, while those that cannot are eliminated.

Peripheral Tolerance: Mechanisms that maintain immune tolerance outside of the central organs, preventing activated lymphocytes from attacking self-tissues in the periphery.